The diagnosis and at times the treatment of recurring right upper quadrant abdominal pain can be quite difficult. All physicians deal with patients having pain in this area and in whom the usual diagnostic tests are negative. The conditions that can cause right upper quadrant pain are multiple. A partial list includes cholecystitis, cholelithiasis (i.e., microlithias), irritable bowel syndrome, esophagitis, biliary dyskinesia and right lower lobe pneumonitis.
Transabdominal ultrasound (TUS) has been considered the "gold standard" in the diagnosis of cholecystitis and choletithiasis until fairly recently. However, the diagnosis of cholecystitis and choletithiasis has proved difficult even when a transabdominal ultrasound instrument is used. As such, many patients experiencing recurring right upper quadrant abdominal pain due to cholecystitis or choletithiasis simple go undiagnosed and continue to explore other reasons for their discomfort.
In an article by Dahan P., et al., Is Endoscopic Ultrasonography (EUS) Helpful in Patients with Suspicion of Complicated Gallstones and Normal Ultrasonography (US), AGA Abstracts, April 1993, pg. A358, it was initially reported that endoscopic ultrasound (EUS) has a sensitivity of 81% in diagnosing cholecystitis in patients with negative transabdominal ultrasound examinations. Dahan et al. further disclosed the use of intramuscular cholecystokinin (CCK) to facilitate biliary drainage in patients when their EUS was negative.
Subsequently, Amouyal, et al., Value of Endoscopic Ultra Sonography in the Diagnosis of Idiopathic Acute Pancreatitis, Gastroenterology, April 1994, Vol. 106, No. 4, Pancreatic Disorders A283, discovered that endoscopic ultrasonography was accurate in demonstrating minilithiasis in the gallbladder in patients with acute idiopathic pancreatitis. In an article by Indaram, S. Channapragrade, A Retrospective Analysis of the Role of Endoscopic Ultrasound in the Evaluation of Gallbladder Diseases, Gastrointestinal Endoscopy No. 200, Vol. 40, No. 2, Part 2, March/April 1994, acalculous cholecystitis with thick sludge or choletithiasis was found in 16 out of 25 patients on endoscopic ultrasound, i.e., 64% sensitivity.
Although combined endoscopic ultrasound and stimulated biliary drainage has been used to diagnose cholecystitis in patients who otherwise would go undetected, it would be highly desirable to develop a diagnostic procedure which would significantly improve such diagnosis from the 81% sensitivity or success rates disclosed in the literature.
The present inventors have developed a unique diagnostic procedure which allows for the use of endoscopic ultrasound and stimulated biliary drainage using an intravenously delivered cholecystokinin analogue in the diagnosis of cholecystitis with an accuracy or sensitivity as high as about 98%. The standardized positioning of the ultrasound transducer in the gastric antrum, movement of the transducer against the stomach wall such that the ultrasound has a full view of the gallbladder, calculation of gallbladder ejection fraction, measuring the contractions of the gallbladder, and ejection of bile fractions using intravenous Kinevac.TM., a cholecystokinin analogue, manufactured by Bristol-Myers Squibb, all combine to provide a higher accuracy or sensitivity rate than earlier combined EUS and biliary drainage methods. One problem discovered with the earlier EUS diagnostic procedures is that they provided cholecystokinin (CCK) intramuscularly which does not appear to cause contraction of the gallbladder which is one of the techniques used by the present inventors to greatly improve the sensitivity of their diagnostic procedure. Two additional diagnostic steps of the present invention which also contribute to the high accuracy or sensitivity of this diagnostic procedure are the visualization of sludge in the gallbladder on endoscopic ultrasound, combined with searching for cholesterol crystals or calcium bilirubinate granules in the ejected bile fractions microscopically. Still other steps which assist in this diagnosis are focal wall thickening, calculation of ejection fractions, and the presence of adhesions.
The present invention also provides many additional advantages which shall become apparent as described below.